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Parasitic diseases caused by kinetoplastid parasites are a burden to public health throughout tropical and subtropical regions of the world. TriTrypDB ( https://tritrypdb.org ) is a free online resource for data mining of genomic and functional data from these kinetoplastid parasites and is part of the VEuPathDB Bioinformatics Resource Center ( https://veupathdb.org ). As of release 59, TriTrypDB hosts 83 kinetoplastid genomes, nine of which, including Trypanosoma brucei brucei TREU927, Trypanosoma cruzi CL Brener and Leishmania major Friedlin, undergo manual curation by integrating information from scientific publications, high-throughput assays and user submitted comments. TriTrypDB also integrates transcriptomic, proteomic, epigenomic, population-level and isolate data, functional information from genome-wide RNAi knock-down and fluorescent tagging, and results from automated bioinformatics analysis pipelines. TriTrypDB offers a user-friendly web interface embedded with a genome browser, search strategy system and bioinformatics tools to support custom in silico experiments that leverage integrated data. A Galaxy workspace enables users to analyze their private data (e.g., RNA-sequencing, variant calling, etc.) and explore their results privately in the context of publicly available information in the database. The recent addition of an annotation platform based on Apollo enables users to provide both functional and structural changes that will appear as ‘community annotations’ immediately and, pending curatorial review, will be integrated into the official genome annotation.

Multiple strategies involving the parasite-host-vector triad are necessary to control leishmania sis. One option is to prevent or reduce transmission of the pathogen by the phlebotomine sand fly vectors. In this sense, it is essential to explore compounds that may influence the vectorial capacity of the insect and reduce its longevity. We investigated the effect of anti- Leishmania drugs administered via the sugar meal on longevity, blood feeding, oviposition, and parasite load on the third day of infection of the sand flies, to identify the most promising candidates for vector infection tests. We identified compounds that affected the longevity of sand flies (three pterocarpanquinones – LQB-475, LQB-181, and LQ-03; one hydroxyethylpiperazine, PMIC-4, and Pentamidine), reduced oviposition of females after blood feeding (LQB-181 and PMIC-4), but did not decrease infection rates or parasite loads. The results provide the effect of antiparasitic drugs from the perspective of the insect vector.

Vector age and survival directly influence vectorial capacity and disease transmission potential. Current age-grading techniques for phlebotomine sand flies are time-intensive and destructive as they require dissection by highly skilled laboratory personnel that groups hematophagous females as young or old depending on parity status. This study examined the potential of near-infrared spectroscopy (NIRS) to age-grade Phlebotomus papatasi sand flies, a primary vector of Leishmania major , a causative agent of cutaneous leishmaniasis. Female (n = 746) and male (n = 497) adult P. papatasi were collected 7, 14, and 21 days post-emergence. The NIR spectra from individual sand flies were used to develop a partial least squares regression model using a leave one out cross-validation approach. Independent test sets of P. papatasi were used to test the model prediction accuracy. When categorized as < 7 or ≥ 7 days old, the overall predictive accuracy was 85% for females and 87% for males. Sand flies reared in slightly cooler insectary conditions were also predicted with greater than 80% accuracy on average. For the first time, this study validates the use of NIRS as a non-destructive and rapid age-grading technique for P. papatasi

Aedes aegypti and Anopheles gambiae harbor the causative agents of diseases such as dengue fever and malaria, afflicting human morbidity and mortality worldwide. Given the worldwide emergence of resistance to insecticides, the current mainstay for vector control, identification of alternative modes of action for future insecticides is paramount. The serotonergic (5-HT) system has been documented to impact physiological mechanisms involved in disease transmission, suggesting its potential as a new mode of action target for future insecticide development. Target 5-HT receptors were cloned and expressed in the HEK293 cell line for functional and pharmacological characterization. Manipulation of the 5-HT system through microinjection of compounds suggests its involvement in the modulation of flight performance and blood-feeding behavior. By attenuating these two determinants of vectorial capacity, transmission and burden of disease could effectively be reduced. Considering these positive global health implications, the 5-HT system is a compelling target for the novel insecticide pipeline.

A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease, specifically with regard to pathology, infection level, and host cytokine levels was conducted. Infection in the absence or presence of saliva in naïve mice was compared. In addition, infection in mice pre-exposed to uninfected vector saliva was compared to infection in unexposed mice. To control for differences in vector and pathogen species, mouse strain, and experimental design, a random effects model was used to compare the ratio of the natural log of the experimental to the control means of the studies. Saliva was demonstrated to enhance pathology, infection level, and the production of Th2 cytokines (IL-4 and IL-10) in naïve mice. This effect was observed across vector/pathogen pairings, whether natural or unnatural, and with single salivary proteins used as a proxy for whole saliva. Saliva pre-exposure was determined to result in less severe leishmaniasis pathology when compared with unexposed mice infected either in the presence or absence of sand fly saliva. The results of further analyses were not significant, but demonstrated trends toward protection and IFN-γ elevation for pre-exposed mice.

Background Phlebotomus papatasi is considered the primary vector of Leishmania major parasites that cause zoonotic cutaneous leishmaniasis (ZCL) in the Middle East and North Africa. Phlebotomus papatasi populations have been studied extensively, revealing the existence of different genetic populations and subpopulations over its large distribution range. Genetic diversity and population structure analysis using transcriptome microsatellite markers is important to uncover the vector distribution dynamics, essential for controlling ZCL in endemic areas. Methods In this study, we investigated the level of genetic variation using expressed sequence tag-derived simple sequence repeats (EST-SSRs) among field and colony P. papatasi samples collected from 25 different locations in 11 countries. A total of 302 P. papatasi sand fly individuals were analyzed, including at least 10 flies from each region. Results The analysis revealed a high-level population structure expressed by five distinct populations A through E, with moderate genetic differentiation among all populations. These genetic differences in expressed genes may enable P. papatasi to adapt to different environmental conditions along its distribution range and likely affect dispersal. Conclusions Elucidating the population structuring of P. papatasi is essential to L. major containment efforts in endemic countries. Moreover, the level of genetic variation among these populations may improve our understanding of Leishmania –sand fly interactions and contribute to the efforts of vaccine development based on P. papatasi salivary proteins. Graphical Abstract

Background The dynamics of vector-borne disease transmission depend on the abundances of vectors. The dominant malaria vector species complex of Anopheles gambiae sensu lato is a target of vector control strategies designed to reduce and eliminate malaria transmission. The three most widely distributed dominant malaria vectors within the species complex are An. arabiensis , An. coluzzii and An. gambiae sensu stricto. Methods Previous studies across the extent of the species complex range have been restricted to annual predictions of species occurrence or relative abundance. This study incorporated relative abundance data at the species level and abundance data at the species complex level to estimate and predict daily equilibrium vector abundances of each species. Statistical models with interpretable parameters were used to gain insight into how factors such as meteorological conditions, insecticide-treated net use and human density affect the spatial and temporal predictions. The statistical models were used to predict daily equilibrium vector abundance, which is an important factor in indices of malaria transmission such as the basic reproduction number and vectorial capacity. Results Meteorological factors, such as precipitation and relative humidity, and human factors, such as population density and insecticide-treated nets, were important predictors of these three malaria vector species in Africa. Insecticide-treated net use was negatively associated with per capita vector abundance of the An. gambiae species complex and interacted with year to suggest a negative effect on the ratio of An. gambiae s.s. to An. arabiensis at the end of the prediction period that extended from 2002 to 2020. A predicted increasing interannual trend for An. coluzzii was potentially caused by changing species identification methods. Conclusions The predicted equilibrium abundances of the three species showed potentially high levels of geographical overlap, niche overlap and evidence for stable coexistence despite substantial interspecific competition. Improving collection of longitudinal species abundance data across the spatial range of the An. gambiae species complex will facilitate future explorations of causal hypotheses that relate vector abundance to control measures, malaria interventions and meteorological conditions.

Phlebotomine sand flies are the subject of much research because of the role of their females as the only proven natural vectors of Leishmania species, the parasitic protozoans that are the causative agents of the neglected tropical disease leishmaniasis. Activity in this field was highlighted by the eighth International Symposium on Phlebotomine Sand flies (ISOPS) held in September 2014, which prompted this review focusing on vector control. Topics reviewed include: Taxonomy and phylogenetics, Vector competence, Genetics, genomics and transcriptomics, Eco-epidemiology, and Vector control. Research on sand flies as leishmaniasis vectors has revealed a diverse array of zoonotic and anthroponotic transmission cycles, mostly in subtropical and tropical regions of Africa, Asia and Latin America, but also in Mediterranean Europe. The challenge is to progress beyond descriptive eco-epidemiology, in order to separate vectors of biomedical importance from the sand fly species that are competent vectors but lack the vectorial capacity to cause much human disease. Transmission modelling is required to identify the vectors that are a public health priority, the ones that must be controlled as part of the integrated control of leishmaniasis. Effective modelling of transmission will require the use of entomological indices more precise than those usually reported in the leishmaniasis literature.

Phlebotomine sand flies employ an elaborate system of pheromone communication wherein males produce pheromones that attract other males to leks (thus acting as an aggregation pheromone) and females to the lekking males (sex pheromone). In addition, the type of pheromone produced varies among populations. Despite the numerous studies on sand fly chemical communication, little is known of their chemosensory genome. Chemoreceptors interact with chemicals in an organism’s environment to elicit essential behaviors such as the identification of suitable mates and food sources. Thus, they play important roles during adaptation and speciation. Major chemoreceptor gene families, odorant receptors (ORs), gustatory receptors (GRs) and ionotropic receptors (IRs) together detect and discriminate the chemical landscape. Here, we annotated the chemoreceptor repertoire in the genomes of Lutzomyia longipalpis and Phlebotomus papatasi , major phlebotomine vectors in the New World and Old World, respectively. Comparison with other sequenced Diptera revealed a large and unique expansion where over 80% of the ~140 ORs belong to a single, taxonomically restricted clade. We next conducted a comprehensive analysis of the chemoreceptors in 63 L . longipalpis individuals from four different locations in Brazil representing allopatric and sympatric populations and three sex-aggregation pheromone types (chemotypes). Population structure based on single nucleotide polymorphisms (SNPs) and gene copy number in the chemoreceptors corresponded with their putative chemotypes, and corroborate previous studies that identified multiple populations. Our work provides genomic insights into the underlying behavioral evolution of sexual communication in the L . longipalpis species complex in Brazil, and highlights the importance of accounting for the ongoing speciation in central and South American Lutzomyia that could have important implications for vectorial capacity.

Phlebotomine sand flies are the vectors of leishmaniasis, a neglected tropical disease. High-quality reference genomes are an important tool for understanding the biology and eco-evolutionary dynamics underpinning disease epidemiology. Previous leishmaniasis vector reference sequences were limited by sequencing technologies available at the time and inadequate for high-resolution genomic inquiry. Here, we present updated reference assemblies of two sand flies, Phlebotomus papatasi and Lutzomyia longipalpis . These chromosome-level assemblies were generated using an ultra-low input library protocol, PacBio HiFi long reads, and Hi-C technology. The new P. papatasi reference has a final assembly span of 351.6 Mb and contig and scaffold N50s of 926 kb and 111.8 Mb, respectively. The new Lu. longipalpis reference has a final assembly span of 147.8 Mb and contig and scaffold N50s of 1.09 Mb and 40.6 Mb, respectively. Benchmarking Universal Single-Copy Orthologue (BUSCO) assessments indicated 94.5% and 95.6% complete single copy insecta orthologs for P. papatasi and Lu. longipalpis . These improved assemblies will serve as an invaluable resource for future genomic work on phlebotomine sandflies.